20 results about "SOX2" patented technology

The invention discloses a biomarker for accurate typing of esophageal squamous carcinoma lesion and application of the biomarker, and belongs to the technical field of molecular biology, the biomarker is SOX2 protein and KDM4B protein which are co-localized in nuclei, and the biomarker is applied to accurate typing of esophageal squamous carcinoma lesion with a non-diagnostic purpose. The cell proportion and distribution conditions of the SOX2 protein and the KDM4B protein are simultaneously displayed on the same section by adopting a double-label immunofluorescence method, and tests prove that the intranuclear co-localization of the SOX2 and the KDM4B can be used as an early warning mark and is used for identifying high-risk patients or early stages of precancerous lesions or distinguishing tumor patients, so that the missed diagnosis rate is reduced, and the diagnosis time is shortened. Therefore, a reliable basis is provided for accurate typing of esophageal squamous carcinoma lesions.

The invention relates to the technical field of biological medicine, and relates to a polypeptide in targeted combination with SOX2 protein and application thereof, the polypeptide has an amino acid sequence as shown in SEQ ID NO.1, or has at least 85%, 90%, 95% or more than 99% of sequence identity with the amino acid sequence; the polypeptide inhibits phase separation of SOX2, liquid drops formed by phase separation of SOX2 can be avoided, then the situation that the liquid drops wrap chemotherapeutic drugs, influence the curative effect of the chemotherapeutic drugs and cause tolerance of tumor cells to the chemotherapeutic drugs is avoided, and the polypeptide does not influence the transcription activation function of SOX2 serving as a transcription factor; the polypeptide can inhibit the phase separation of the SOX2, so that the regulation of normal physiological functions, such as high expression in organs such as eyes of a human body, of the SOX2 as a transcription factor is not influenced, and therefore, the polypeptide disclosed by the invention can reverse chemotherapy drug resistance of tumors such as squamous carcinoma by inhibiting the phase separation of the SOX2, can be used for adjuvant therapy of the tumors such as squamous carcinoma, and has no obvious toxic or side effect on each organ of an organism.

Disclosed is an efficient and non-genetically modified iPSC-induced, industrialized single clone selection platform, and a use. The platform can efficiently perform reprogramming, and only requires the use of a minimal number of reprogramming factors (OCT4, SOX2, E6, E7). During the single clone separation stage of the present invention, SSEA4 / TRA-1-60 is used as a screening marker, and a large number of single cell clones are obtained by means of flow cytometry. The platform described in the present invention has advantages such as high reprogramming efficiency, high safety, easy operation, and large-scale production.

The application discloses a kind of compositions and applications for regenerating retinal ganglion cells by using endogenous microglia.The present application finds that multiple genes (Brn3b, Sox2, Cbln1 and NP1, referred to as BSCN) can be expressed in microglia to transform into retinal ganglion cells by in vivo microglia fate lineage tracking.The regenerated ganglion cells project axons to the distant brain, rebuild visual neural circuit and restore impaired vision in adult glaucoma mice.In addition, the regenerated ganglion cells can stably survive for up to one year, and the same regeneration strategy is used in old glaucoma mice, which confirms the effectiveness of BSCN reprogramming to regenerate RGCs.Therefore, the present application determines that microglia is a new type of reprogramming seed cell, and finds that four key genes are involved in RGCs regeneration to restore vision, which provides a new therapeutic drug and means for the treatment of glaucoma and related diseases.

The present invention relates to a composition for the prevention or treatment of cisplatin-resistant cancer comprising an inhibitor of DUSP23 expression or activity as an active ingredient. It was found that DUSP23 expression is upregulated in cell clusters exhibiting characteristics of cancer stem cells, and that knocking down DUSP23 significantly reduces cell cluster formation as well as decreases the expression of SOX2, a major stem cell marker. Furthermore, DUSP23 expression was increased in lung cancer cells that had developed cisplatin resistance, and it was confirmed that the downregulation of DUSP23 inhibits self-renewal and invasive capabilities during the induction of cancer cell death. In addition, it was confirmed that DUSP23 plays an important role in promoting cancer stem cell characteristics through SOX2 expression. In conclusion, it has been shown that targeting DUSP23 can be a promising therapeutic strategy to overcome anticancer drug resistance in lung cancer, and the composition of the present invention is expected to be usefully utilized as a treatment for lung cancer cells with cisplatin resistance.

The present invention relates to a single domain antibody specifically binding to STAT3 or an antigen-binding fragment thereof, a fusion protein comprising the single domain antibody or the antigen-binding fragment thereof, and a use of the fusion protein.

The invention discloses a culture medium for goat trophoblast organoid, a culture method and application, and belongs to the field of goat trophoblast organoid culture. The method comprises the following steps: separating trophoblast tissues from a healthy goat placenta which is pregnant for 80-90 days, digesting the trophoblast tissues through type II collagenase to obtain primary cells, compounding the primary cells with matrigel, and performing three-dimensional culture in an improved trophoblast organ culture medium with specific components to form mature organs. The organ is of a typical three-dimensional structure, and KRT23 and SOX2 markers are stably expressed. The organoid culture system based on the goat primary trophoblast cells is established for the first time, gene modification is not needed, the in-vivo physiological status is highly simulated, and the culture system is standardized and good in repeatability. The constructed organoid can be used as an ideal in-vitro model for researching placenta development, evaluating drugs and toxins and modeling infectious diseases in the gestation period, and is of great significance in improving the reproductive research level of goats and the production benefits of animal husbandry.

The present invention relates to a method for directing differentiation of ventral midbrain NSCs into neurons comprising contacting a cell population comprising ventral midbrain NSCs with an inhibitor of MEK signaling and an inhibitor of NOTCH signaling, wherein the ventral midbrain NSCs co-express the markers FOXA2, LMX1A, EN1, OTX2, 5 and SOX2.

Animal cells, notably adult fibroblasts, are advantageously reprogrammed in direct lineage reprogramming methods using defined factors to produce proliferative and multipotent induced cardiac progenitor cells (iCPC). The iCPC thus produced can be differentiated under suitable differentiation conditions to cardiac lineage cells including cardiomyocytes, smooth muscle cells, and endothelial cells, as evidenced by expression of lineage specific markers. Sets of factors effective in combination to reprogram the fibroblasts can include a set that includes some or all of 5 factors (Mespl, Baf60c, Nkx2.5, Gata4, Tbx5), a set that includes some or all of 11 factors (Mespl, Mesp2, Gata4, Gata6, Baf60c, SRF, Isll, Nkx2.5, Irx4, Tbx5, Tbx20), a set that includes some or all of 18 factors (T, Mespl, Mesp2, Tbx5, Tbx20, Isll, Gata4, Gata6, Irx4, Nkx2.5, Handl, Hand2, Tbx20, Tbx18, Tip60, Baf60c, SRF, Hey2), and a set that includes some or all of 22 factors (T, Mespl, Mesp2, Tbx5, Tbx20, Isll, Gata4, Gata6, Irx4, Nkx2.5, Hand1, Hand2, Tbx20, Tbx18, Tip60, Baf60c, SRF, Hey2, Oct4, Klf4, Sox2, L-myc).

Methods are provided for generating pancreatic endocrine cells from pluripotent stem cells (PSCs) using epigenetic modifiers. A fusion protein comprising catalytically inactivated Cas9 (dCas9) and an embryonic ectoderm development (EED)-binding domain (EBdCas9) is used with guide RNAs (gRNAs) to target regulatory regions of transcriptional regulators including EOMES, PDX1, and NGN3. Sequential targeting of PDX1 and NGN3 promoters with EBdCas9 removes repressive H3K27me3 marks, increases activating H3K27ac modifications, and accelerates differentiation into insulin-producing β-cells. The methods significantly increase β-cell yields (~4-6 fold), reduce non-pancreatic lineage contaminants (CDX2+, SOX2+, enteroendocrine cells), enhance mitochondrial function, and produce glucose-responsive cells with superior functional maturation in vivo. The epigenetic interventions enforce pancreatic developmental fates while activating NGN3-dependent transcriptional programs necessary for endocrine cell differentiation, insulin secretion, and metabolic maturation. Cells and compositions produced by these methods are also provided.

The invention discloses application of H3K9me2 as a target spot in preparation of a preparation for inducing stem cells to differentiate to gametes in vitro, and relates to the technical field of stem cell breeding in animal husbandry. An H3K9me2 inhibitor BIX01294 is adopted as a treating agent, and in-vivo treatment is performed on a pregnant mouse and in-vitro treatment is performed on gonad tissue of a female fetal mouse. The result shows that the BIX01294 treatment can cause the reduction of the expression level of H3K9me2, so that the expression levels of pluripotent genes Oct4, Sox2 and Dppa3 are increased, the accessibility of whole genome chromatin is obviously changed, and the meiosis start and meiosis process are blocked. The result shows that the H3K9me2 can influence the differentiation of the stem cells to the gametes and is beneficial to the generation of artificial gametes in the stem cell breeding process.

The present invention provides methods of transdifferentiating a somatic cell, e.g., a fibroblast, to an induced dopaminergic precursor cell (iDP) in vitro. The methods include ectopically expressing genes of (1) one or both of Brn2 and Brn4, or a variant thereof, (2) Sox2, or a variant thereof, and (3) one or both of Foxa2 and Lmx1a, or a variant thereof, in the somatic cell, and methods for treating a neurodegenerative disease, such as Parkinson's disease, with the iDP.

Provided are a cow milk-derived stem cell, and an isolation and culture method therefor. The method comprises the following steps: (1) taking fresh cow milk, and isolating cells therefrom; (2) coating a culture dish with a matrix gel in advance, discarding the coating solution, then washing the culture dish with a washing solution, and discarding the washing solution; (3) inoculating the cells treated in the step (1) on the coated culture dish, and culturing the cells with a stem cell culture medium; and (4) when the cell confluence reaches 80% or more, digesting the cells with a digestion enzyme, terminating the digestion, isolating the cells, resuspending the cells using a CTFR culture solution, then inoculating the cells on a feeder layer for culture, promoting colony formation, and performing subculture to obtain cow milk-derived stem cells. The cow milk-derived stem cell has OCT4, SOX2, NANOG and SSEA4 markers.

The present invention relates to a single domain antibody specifically binding to STAT3 or an antigen-binding fragment thereof, a fusion protein comprising the single domain antibody or the antigen-binding fragment thereof, and a use of the fusion protein.

Provided are designed proteins, derived from OCT4 and SOX2, which have enhanced stability and binding affinity for one another compared to the wild-type equivalents. These designed proteins are species-agnostic. Specifically provided are isolated SOX2 proteins having an artificial SOX2 DNA binding domain and isolated OCT4 proteins having an artificial OCT4 DNA binding domain. Also provided are uses of these proteins to generate induced pluripotent stem cells, vectors, and host cells containing these proteins.

The invention discloses an efficient and safe fibroblast reprogramming method and system, and belongs to the field of cell reprogramming. The method comprises the following steps: firstly, constructing a CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) activation system, namely constructing dCAS-VPR fusion protein and designing sgRNA (Ribonucleic Acid) of a regulation region targeting OCT4 and SOX2 genes; secondly, introducing the system into somatic cells through an electroporation method; and finally, performing induction by adding chemical small molecule combinations in stages, including adding a histone deacetylase inhibitor and a TGF-beta pathway inhibitor into a culture medium in a stage I and adding a Wnt activator into a culture medium in a stage II, so as to finally obtain the induced pluripotent stem cells. According to the method, the reprogramming efficiency is improved by more than 20 times, the period is shortened to be within 16 days, the exogenous gene integration risk is completely avoided, and a safe and efficient solution is provided for individualized treatment.

The invention belongs to the technical field of biological medicines, and particularly discloses an induced pluripotent stem cell (iPSC) strain carrying ABCB4 gene mutation and application thereof. The stem cell strain is preserved in the China Center for Type Culture Collection (the preservation number is CCTCC NO: C2025125), and carries ABCB4 gene composite heterozygous mutation c.992Ggt; a is (p.G331E), and c is 3152Tgt; the invention relates to the field of biomarkers (p.V1051A, C (p.V1051A), which can stably express pluripotent markers (OCT4, SOX2, NANOG and SSEA4), and has the capability of differentiating towards trigerm layers. The stem cell strain can be used for constructing a research model of progressive familial intrahepatic cholestasis type 3 (PFIC3), simulates disease phenotypes by differentiating hepatic cells or bile duct cells, is suitable for drug screening and gene therapy research, and provides a precise humanized tool for mechanism analysis and treatment development of ABCB4 mutation related diseases.

Oncolytic HSV vectors comprising NF-κB response elements or Oct-3 / 4-SOX2 response elements in the regulatory regions of viral genes that affect the efficiency of viral replication.

This invention discloses a method for inducing mouse embryonic stem cells to transition to a pluripotent state using H2BC21 and its application, belonging to the fields of molecular biology and stem cell engineering technology. By constructing an interference vector targeting the H2BC21 gene, packaging it with lentivirus, and infecting mouse embryonic stem cells, the expression of the H2BC21 gene is knocked down, and embryonic stem cell lines with stable low expression of H2BC21 are obtained through screening. This invention is the first to discover that H2BC21 is a core negative regulator of mammalian embryonic stem cell pluripotency. After knocking down H2BC21, the expression of pluripotency core genes Nanog, Oct4, and Sox2 is downregulated, while the expression of pluripotency core genes Zscan4b, Usp17la, and Tmem92 is upregulated. The cells exhibit molecular characteristics similar to 2-cell phase cells, successfully achieving the transition from pluripotency to a pluripotent state.

This invention relates to the field of cell dedifferentiation, and more particularly to a method for promoting the dedifferentiation of satellite glial cells into neural stem cell-like cells. First, a three-dimensional composite hydrogel of nervonic acid-modified chitosan is constructed. Then, satellite glial cells are seeded and cultured in this hydrogel, inducing dedifferentiation to obtain a cell population with a neural stem cell-like phenotype. The hydrogel constructs a basic network through covalently linked amide bonds between nervonic acid and chitosan, and utilizes the hydrophobic association domains formed by the long-chain alkyl groups of nervonic acid to self-assemble into a covalently cross-linked + hydrophobically associated dual network structure. This simulates the softness, deformability, and local mechanical gradient properties of the neural tissue microenvironment, providing ideal dedifferentiation conditions for satellite glial cells to differentiate into neural stem cell-like cells. During the dedifferentiation process, markers such as Nestin, SOX2, and PAX6 are expressed, showing promising applications in neural regeneration, disease model construction, and cell therapy.